Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD August 2015 CONTENTS General Toxicology 6 Metals 34 Management 17 Pesticides 35 Drugs 19 Chemical Warfare 38 Chemical Incidents & 28 Plants 39 Pollution Chemicals 29 Animals 39 CURRENT AWARENESS PAPERS OF THE MONTH Child poisonings with methadone in France: a 6-year prospective national survey since the availability of capsules in 2008 Torrents R, Picot C, Glaizal M, Courne M-A, Schmitt C, Richard N, Simon N, Cardona F, de Haro L. Clin Toxicol 2015; 53: 819-22. Background Methadone for opiate substitution was available only in syrup formulation prior to 2008. In 2007, the French Health Authorities made solid forms available. A national survey was performed in order to evaluate the modification of child poisonings induced by such a new pharmaceutical formulation. Methods A prospective study was set up (April 15, 2008 to April 15, 2014) with the analysis of cases of unintentional ingestion of methadone by patients under 18 years old and managed by the 10 French poison control centers at the national level. As soon as a new pediatric exposure was recorded in the informatics data bank of the Poison Centers, a telephone survey was performed by the Marseilles' Poison Center to obtain the evolution and all the necessary details. Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units. The NPIS is commissioned by Public Health England 2 Results 87 cases of child poisonings with the 2 forms were reviewed (syrup, 56 patients; capsules, 31 patients). Comparison shows that patients were similar for both formulations (no significant difference concerning age [median 2 years], sex ratio [M/F 0.85], previous history, and ingested quantities of methadone). There was a similar severity profile with both formulations proving that methadone can lead to lethal child intoxications (1 death with capsules and 4 with syrup). The relative risk of pediatric accidents is also the same with 2 formulations, leading the health authorities, in collaboration with laboratories, to design and distribute flyers. The aim was to inform patients who are also parents about the high danger risk of their treatment for children, whatever the formulation of methadone present in the house. Discussion The results of this survey were similar to those of another national study by the French Poison Centers concerning adult suicide attempts with methadone. Both prospective studies led to the conclusion that methadone must be considered as a dangerous molecule for patients and their families. The recent availability of a solid formulation in France did not change the profile of poisonings with this opiate substitute treatment. Full text available from: http://www.tandfonline.com/doi/full/10.3109/15563650.2015.1073298#abstract External validation of the paracetamol-aminotransferase multi- plication product to predict hepatotoxicity from paracetamol overdose Wong A, Sivilotti MLA, Dargan PI, Wood DM, Greene SL. Clin Toxicol 2015; 53: 807-14. Context Risk prediction in paracetamol (acetaminophen, or APAP) poisoning treated with acetylcysteine helps guide initial patient management and disposition. The paracetamol-aminotransferase multiplication product may be a useful and less time-sensitive risk predictor. Objective The aim of this study was to validate this multiplication product in an independent cohort of patients with paracetamol overdose. Materials and methods Using an existing toxicology dataset of poisoned patients from two large inner-city United Kingdom teaching hospitals, we retrospectively identified by electronic search all paracetamol overdoses from February 2005 to March 2013. We assessed the diagnostic accuracy of the multiplication product (serum APAP concentration × alanine transaminase [ALT] activity), especially at the pre-specified cut-off points of 1 500 mg/L × IU/L (10 000 micromol/L × IU/L) and 10 000 mg/L × IU/L (66 000 micromol/L × IU/L). The primary outcome was hepatotoxicity defined by a peak ALT > 1000 IU/L. Results Of 3823 total paracetamol overdose presentations, there were 2743 acute single, 452 delayed single (> 24 h post overdose), 426 staggered (ingestion over > 1 h), and 202 supratherapeutic ingestions. Altogether, 34 patients developed hepatotoxicity. Among the acute single-ingestion patients, a multiplication product > 10 000 mg/L × IU/L had a sensitivity of 80% (95% confidence interval [CI]: 44%, 96%) and specificity of 99.6% [99.3%, 99.8%], while a product > 1 500 mg/L × IU/L had a sensitivity of 100% [66%, 3 100%] and specificity of 92% [91%, 93%]. Overall, 16 patients with a multiplication product > 10 000 mg/L × IU/L developed hepatotoxicity (likelihood ratio: 250, 95% CI: 130, 480), and 4 patients with a multiplication product between 1 500 and 10 000 (likelihood ratio: 2.5, 95% CI: 1.0, 6.0). No patient with a product < 1 500 mg/L × IU/L who received acetylcysteine developed hepatotoxicity. Conclusions Regardless of ingestion type, a product > 10 000 mg/L × IU/L was associated with a very high likelihood, and < 1 500 mg/L × IU/L with a very low likelihood, of developing hepatotoxicity in patients treated with acetylcysteine. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1066507 Pharmacological treatment of acquired QT prolongation and torsades de pointes Thomas SHL, Behr ER. Br J Clin Pharmacol 2015; online early: doi: 10.1111/bcp.12726: Abstract and full text available from: http://dx.doi.org/10.1111/bcp.12726 Confusion about infusion: rational volume limits for intravenous lipid emulsion during treatment of oral overdoses Fettiplace MR, Akpa BS, Rubinstein I, Weinberg G. Ann Emerg Med 2015; 66: 185-8. Full text available from: http://dx.doi.org/10.1016/j.annemergmed.2015.01.020 Intravenous lipid emulsion therapy for severe diphenhydramine toxicity: a randomized, controlled pilot study in a swine model Varney SM, Bebarta VS, Boudreau SM, Vargas TE, Castaneda M, Zarzabal LA. 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